Jun Yoshino

Mechanisms of Direct Inhibitory Action of Isoflurane on Vascular Smooth Muscle of Mesenteric Resistance Arteries

Background Isoflurane has been shown to directly inhibit vascular reactivity. However, less information is available regarding its underlying mechanisms in systemic resistance arteries. Methods Endothelium-denuded smooth muscle strips were prepared from rat mesenteric resistance arteries. Isometric force and intracellular Ca2+ concentration ([Ca2+]i) were measured simultaneously in the fura-2-loaded strips, whereas only the force was measured in the &bgr;-escin membrane-permeabilized strips. Results Isoflurane (3–5%) inhibited the increases in both [Ca2+]i and force induced by either norepinephrine (0.5 &mgr;m) or KCl (40 mm). These inhibitions were similarly observed after depletion of intracellular Ca2+ stores by ryanodine. Regardless of the presence of ryanodine, after washout of isoflurane, its inhibition of the norepinephrine response (both [Ca2+]i and force) was significantly prolonged, whereas that of the KCl response was quickly restored. In the ryanodine-treated strips, the norepinephrine- and KCl-induced increases in [Ca2+]i were both eliminated by nifedipine, a voltage-gated Ca2+ channel blocker, whereas only the former was inhibited by niflumic acid, a Ca2+-activated Cl− channel blocker. Isoflurane caused a rightward shift of the Ca2+-force relation only in the fura-2-loaded strips but not in the &bgr;-escin-permeabilized strips. Conclusions In mesenteric resistance arteries, isoflurane depresses vascular smooth muscle reactivity by directly inhibiting both Ca2+ mobilization and myofilament Ca2+ sensitivity. Isoflurane inhibits both norepinephrine- and KCl-induced voltage-gated Ca2+ influx. During stimulation with norepinephrine, isoflurane may prevent activation of Ca2+-activated Cl− channels and thereby inhibit voltage-gated Ca2+ influx in a prolonged manner. The presence of the plasma membrane appears essential for its inhibition of the myofilament Ca2+ sensitivity.

Intraoperative changes in arterial oxygenation during volume‐controlled mechanical ventilation in modestly obese patients undergoing laparotomies with general anesthesia

Background:   In obese patients, arterial oxygenation can be greatly impaired during general anesthesia. Both avoidance of denitrogenation and application of positive end‐expiratory pressure (PEEP) during mechanical ventilation may be effective in preventing such impairment of arterial oxygenation.

The Perioperative Complications for Elderly Patients with Lung Cancer Associated with a Pulmonary Resection Under General Anesthesia

Background: Surgery for elderly patients with lung cancer is relatively common due to the increasing elderly population. This study evaluated the perioperative complications associated with surgery in patients over 70 years of age with lung cancer. Patients and Methods: A single-center retrospective evaluation was conducted of perioperative complications (1996-2006) in lung cancer surgical patients. We reviewed and analyzed the clinical records of 364 consecutive patients over 70 years of age and 392 control patients. Results: The mean age of the elderly group was 75.5 years old and that of the control group was 59.4 years. A segmental or wedge resection was performed more frequently for the elderly group than in the control group, whereas pneumonectomies and lobectomies were performed more frequently in the control group. Preoperative comorbidities such as cardiac and thoracic diseases were more frequently recognized in the elderly group than in the control group. The quantity of propofol used as induction anesthesia in the elderly group was significantly smaller than that of the control group, furthermore, the operation time and operation room stay time of the elderly group were significantly shorter than that of the control group, however, extubation time was significantly prolonged. The ratio of thoracic complications in the elderly group was higher than that in the control group. The ratio of pulmonary leakage in the elderly group was higher than in the control group; however, there was no significant difference in length of stay in the hospital, the ratio of operative death and hospital death between the two groups. Conclusions: Elderly patients more frequently have perioperative complications than younger patients; however, there was no statistical difference in mortality. A pulmonary resection for elderly patients may therefore be as feasible as in younger patients.

The mechanisms of the direct action of etomidate on vascular reactivity in rat mesenteric resistance arteries.

BACKGROUND: Etomidate minimally influences hemodynamics at a standard induction dose in young healthy patients, but can cause significant systemic hypotension at higher doses for induction or electroencephalographic burst suppression (i.e., cerebral protection) in patients with advanced age or heart disease, and during cardiopulmonary bypass. However, less is known about its action on systemic resistance arteries. METHODS: Using an isometric force recording method and fura-2-fluorometry, we investigated the action of etomidate on vascular reactivity in small mesenteric arteries from young (7–8 wk old, n = 179) and aged (96–98 wk old, n = 10) rats. RESULTS: In the endothelium-intact strips from young rats, etomidate enhanced the contractile response to norepinephrine or KCl (40 mM) at 3 &mgr;M but inhibited it at higher concentrations (≥10 &mgr;M). The enhancement was still observed after treatment with NG-nitro l-arginine, tetraethylammonium, diclofenac, nordihydroguaiaretic acid, losartan, ketanserin, BQ-123, or BQ-788, but was not observed in aged rats. In the endothelium-denuded strips from young rats, etomidate (≥10 &mgr;M) consistently inhibited the contractile response to norepinephrine or KCl without enhancement at 3 &mgr;M. In the fura-2-loaded, endothelium-denuded strips from young rats, etomidate inhibited norepinephrine- or KCl-induced increases in both intracellular Ca2+ concentration ([Ca2+]i) and force. Etomidate still inhibited the norepinephrine-induced increase in [Ca2+]i after depletion of the intracellular Ca2+ stores by ryanodine, which was sensitive to nifedipine. Etomidate had little effect on norepinephrine- or caffeine-induced Ca2+ release from the intracellular stores or Ca2+ uptake into the intracellular stores. During stimulation with norepinephrine or KCl, etomidate had little effect on the [Ca2+]i-force relation at low concentrations (≤30 &mgr;M) but caused its downward shift at 100 &mgr;M. CONCLUSIONS: In small mesenteric arteries, etomidate influences the contractile response to norepinephrine or membrane depolarization through endothelium-dependent enhancing and endothelium-independent inhibitory actions. The enhancement is at least in part independent of nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, angiotensin II, serotonin, or endothelin-1, but may involve some signaling pathway that is impaired by aging. The endothelium-independent inhibition is due to decreases in both the [Ca2+]i and myofilament Ca2+ sensitivity in vascular smooth muscle cells. The decrease in [Ca2+]i would be due mainly to inhibition of voltage-gated Ca2+ influx. The observed inability of lower concentrations (1–3 &mgr;M) of etomidate to cause significant vasodilation is consistent with minimal changes in hemodynamics during induction of anesthesia with etomidate in young subjects, whereas the observed vasodilator action of higher concentrations of etomidate might underlie systemic hypotension caused by higher doses of etomidate in the clinical setting.

Diabetes-associated Alterations in Volatile Anesthetic Actions on Contractile Response to Norepinephrine in Isolated Mesenteric Resistance Arteries

Background:Clinical concentrations of volatile anesthetics significantly influence contractile response to the sympathetic neurotransmitter norepinephrine although its precise mechanisms remain unclarified. In this study, we investigated its possible alterations in diabetes, as well as its underlying mechanisms. Methods:Isometric force was recorded in small mesenteric arteries from streptozotocin-induced diabetic and age-matched control rats. Results:The concentration–response curve for acetylcholine-induced endothelium-dependent relaxation was shifted to the right in diabetic arteries compared with controls. The concentration–response curve for norepinephrine-induced contraction was shifted to the left and upward by both endothelial denudation and diabetic induction. In the presence of endothelium, isoflurane or sevoflurane enhanced norepinephrine-induced contraction in control arteries but not in diabetic arteries; however, in its absence, both anesthetics identically inhibited norepinephrine-induced contraction in both groups. In control arteries, the isoflurane- or sevoflurane-induced enhancement was not affected by adrenomedullin22–52, calcitonin gene-related peptide8–37, 18&bgr;-glycyrrhetinic acid, NG-nitro l-arginine, ouabain, Ba2+, indomethacin, losartan, ketanserin, BQ-123, and BQ-788. Conclusions:In diabetes, vascular responses to acetylcholine, norepinephrine, and volatile anesthetics are altered in mesenteric resistance arteries, presumably reflecting endothelial dysfunction and possibly underlying circulatory instability during administration of either anesthetic. Some endothelial mechanisms that are impaired in diabetes would be involved in the anesthetic-induced enhancement of norepinephrine-induced contraction. However, the vasoregulatory mechanism mediated by adrenomedullin, calcitonin gene-related peptide, myoendothelial gap junction, nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, angiotensin II, serotonin, or endothelin-1, all of which have been suggested to be impaired in diabetes, would not be involved in the enhancement.

Anesthetic management of a patient with aortocaval fistula

Aortocaval fistula is a rare complication of ruptured abdominal aortic aneurysm (AAA), and patients with an aortocaval fistula show multiple symptoms. We report an 87-year-old man who was diagnosed as having an AAA with aortocaval fistula and who developed refractory hypotension after induction of anesthesia. Following a phenylephrine injection for slight hypotension induced by anesthetic induction, he developed severe hypotension and bradycardia, and his skin became cyanotic. Vasopressor agents had no immediate effect on the hypotension, but blood pressure gradually increased in about 30 min with continuous infusion of dopamine and noradrenaline. Transesophageal echocardiography (TEE) showed right ventricle (RV) hypokinesis and massive tricuspid regurgitation (TR). Central venous pressure (CVP) showed a remarkably high value. After the repair of the aortocaval fistula, the hemodynamics became stable, RV motion was improved, TR was reduced, and CVP became normal. Anesthetic management of the repair of an aortocaval fistula is very difficult. The hemodynamics changed dramatically throughout anesthesia in our patient with this disorder, even though low-dose anesthetics were used. For the successful treatment of this disorder, preparation for the operation is required before the induction of anesthesia, and urgent closure of the fistula is necessary after the induction of anesthesia. TEE is a useful tool for monitoring hemodynamics in such patients.